Calcium-sugar preparation and method of treatment



Patented Nov. 15, 1927.

UNITED STATES PATENT OFFlCE.

GUY VAN SGOYOCyOF SALT LAKE CITY, UTAH, AND HENRY L. WEHRBEIN, OF

INDIANAPOLIS, INDIANA.

CALCIUM-SUGAR PREPARATION AND METHOD OF TREATMENT.

Ho Drawing.

It is the object of our invention to malie it possible to use calcium advantageously m the treatment of disease, with more beneficial eifects and less objectionable efiects than are now obtained in calcium treatment and es pecially to do so in treatment by intravenous injection; and to do this with a calcium product in which the calcium is combined with a substance which is itself readily tolerated in the human body and which permits the beneficial therapeutic effects and substantially prevents the objectionable effects from the calcium.

The use of calcium by intravenous injection is indicated in a number of diseases, es pecially in tuberculosis, and also in hayfever, asthma, urticaria, and others; but with the calcium compounds heretofore mainly used there was a considerable degree of toxicity, a certain lack of bodily tolerance, a lack of complete response to the quantity ofcalcium used, and sometimes disagreeable after eifects such as collapse.

We discovered some time ago that a cal- 36 cium-glucose preparation had certain beneficial effects in relieving certain of the diseases above named, especially tuberculosis, and that product was used with a considerable degree of success. This prior product was directly of calcium and glucose. and in its use it was contemplated that whatever compounds were formed in the product with the calcium should be directly of the glucose, with no thought of any glucose-degradation products; for the product was used intravenously before an degradation of-the lucose by reason of t e presence of the calcium occurred.

We have now discovered that while this product of calcium with unmodified glucose is effective in relieving disease it is not free from certain objectionable efi'ects, particularly onthe walls of the veins in which the intravenous injection is made. We have also found that these eflects on the vein-walls may be avoided by permitting partial degradation of the sugar to occur in the presence of the calcium before the intravenous injection is made, so that the product is at least partially of calcium with certain degradation-products of glucose instead of with glucose itself. If the degradationof the glucose is carried sulficiently far, we find that we substantially eliminate the objectionable 1924. Serial No. 710,433.

effects of the calcium-glucose product, and avoid the undesirable actions on the veinwalls of the patient at and near the point of fects decrease rapidly at first, and largely s disappear before the beneficial therapeutic effects are effected, for the beneficial therapeutic efi'ects diminish little in the early part of such degradation but disappear mainly in the latter part thereof.

Our present invention, therefore, contemplates the use of a product containing calcium and certain products resulting from the partial degradation of sugar in the presence of calcium. The sugar we prefer to use is glucose or dextrose, but we find that we can use any of the varieties of en at in which there is a free aldehyde or etone group, of which the hexoses are the most desirable. We find thatsugars which do not have free aldehyde or ketone groups, such as sucrose, are not suitable, because they form no degradation products in the presence of calcium.

In carrying out our invention, we mix the sugar, most desirably dextrose, with calcium hydroxide, in water. Following this mixing, a certain degradation of the dextrose starts, which de adation will continue through a number 0 intermediate steps to a final complete-degradation product if allowed to continue sufliciently long. This degradation occurs slowly at normal tem ratures, but is greatly hastened by heat. erefore, while we can merely let the mixture stand for a suitable time, it is generally desirable to accelerate the degradation by heat; but the temperature should not reach the boiling point.

This degradation, however, should not be carried too far. To get the desired degradation, and to have the 'roduct at the desired point of sugar-degradation when the intravenous injection is made, we prefer to mix the dextrose and calcium hydroxide shortly before the injection is to be made, and then to heat the mixture until it reaches a rich brown color, but is still transparent; following which we quickly cool, the solution, and

quickly make the desired injection. The

hysician may readily determine this color E the eye, for we believe it is not essential t at the degradation be carried to an exact point. as we find that considerable range in color will remove the objectionable effects while still preserving the beneficial effects. This same color change occurs whether or not heat is used, but it occurs quite slowly in the cold. If other than a mere color determination of the extent of the degradation is desired, it may be obtained by the use of phenolphthalein; the degradation being carried on until the alkalinit of the sugar-caL cium product as measure by phenolphthalein titration is less than one-half that of the original solution, and desirably between 10% and thereof. The partial degradation product thus obtained should be adminlstered promptly after this point of degradation is reached, for if the product is allowed 7 to stand, even in the cold, the degradation continues and the beneficial effects of the calcium are destroyed.

In making our product, we preferably proceed in the followin manner. We preare a water solution of sugar; which may any of the sugars above referred to, though dextrose is preferable. This solution may be of any desired concentration, but is desirably of fairly high concentrationusually from twenty per cent (20%) to twenty-five per cent (25%)so that a considerable quantity of the final sugar-product may be contained in a relatively small volume. To this sugar solution, conveniently at room temperature, we add calcium oxide or calcium hydroxide in less than one molecular weight of calcium hydroxide for one molecular weight of sugar. \Vith dextrose, this means at least two and one half parts by weight of dextrose to one part by weight of calcium hydroxide. We prefer to use rather more sugar than this, however, and find it desirable to use five to fifteen parts by weight of dextrose (for instance) to one art by weight of calcium hydroxide. The ca cium hydroxide is much more soluble in this sugar solution than in water. We then filter to remove undesirable products. While we can let this product stand until the desired degradation occurs, as such degradation occurs spontaneously, we preferably heat the product, to less than'boiling but conveniently fairly close to boiling, until it takes on a rich brown color: and then we quickly cool the solution, and inject it intravenously.

We have found that the product may be dispensed in several ways. the sugar solution (ii water if desired) and the ct lcium hydroxide in separate packages, the contents of which the physician may mix and heat for himself, the heating producing not only the degradation of the sugar but We may dispense also effective sterilization. Probably the advantageous way of dispensing, however, is

that set forth in the co-pending application of ourselves and Horace A. Shonle, Serial No. 710,434, of even filing date herewith;

but as that forms no part of the present inyention, we shall not attempt to describe it ere.

\Ve claim as our invention 1. The method of using calcium intravenously, comprising forming in solution a product of calcium and a partial-degradation product of a sugar containing a free aldehyde or ketone group, and injecting said calcium-sugar product intravenously when said degradation is at an intermediate stage 2. The method set forth in claim 1, with the addition that the sugar is a hexose.

3. The method set forth in claim 1, with the addition that the sugar used is dextrose.

i. The method set forth in claim 1, with the addition that the molecular amount of sugar used exceeds that of calcium.

5. The method set forth in claim 1, with the addition that the sugar used is a hexose, and that the molecular amount of themes used exceeds that of calcium.

6. The method set forth in claim 1, with the addition that the sugar used is dextrose, and that the molecular amount of dextrose used exceeds that of calcium.

7. The method set forth in claim 1, with the addition that the degradation is con:

tinued to a point where the alkalinity of the' product is less than one-half that of the original calcium-sugar product, and that the injection is made before further degradation thereof.

8. The method set forth in claim 1, with the addition that the sugar is a hexose, and that the degradation is continued to a point where the alkalinity of the roduct is less than one-half that of the original calciumhexose product, and that the injection is made before further degradation thereof.

9. The method set forth in claim 1, with the addition that the sugar used is dextrose, and that the degradation is continued to a oint where the alkalinity of the roduct is ess than one-half that of the original calcium-dextrose product, and that the injection is made before further degradation thereof.

10. The method set forth in claim 1, with the addition that the injection is made when the degradation of the su ar has continued sufficiently far to substantially eliminate the ob'ectionable efiects of the calcium' on the ve1n-walls but not sufliciently far to destroy the beneficial effects of the calcium on the disease.

11. The method set forth in claim 1, with the addition that the su r is a hexose, and that the injection is ma e when the degradation of the hexose has continued sufiiciently far to substantially eliminate the objectionable effects of the calcium on the vein-walls but not sufliciently far to destroy the beneficial eifects of the calcium on the disease.

12. The method set forth in claim 1, with the addition that the sugar used is dextrose, and that the injection is made when the degradation of the dextose has continued sufiiciently far to substantially eliminate the objectionable effects of the calcium on the veinwalls but not sufliciently far to destroy the beneficial effects Jf the calcium on the disease.

13. A chemical product, comprising the result obtained by mixing calcium hydroxide with a solution of a sugar having a free aldehyde or ketone group, in the proportion of at least one part by weight of calcium hydroxide to fifteen parts of sugar, and er mitting degradation to proceed under eat until such result has an alkalinity of less than one-half of the alkalinity of the composition at the start of the degradation.

14. The chemical roduct set forth in claim 13, with the a dition that the sugar with which the calcium hydroxide is mixed is a hexose.

15. The chemical product set forth in claim 13, with the addition that the sugar with which the calcium hydroxide is mixed is dextrose.

16. A chemical product, comprising the result obtained by mixing calcium hydroxide with a solution of a sugar having a free aldehyde or ketone group, in the proportion of at least one part by weight of calcium hydroxide to fifteen parts of sugar, and permittin degradation to roceed until such result as an alkalinity less than one-half of the alkalinity of the composition at the start of the degradation.

17. The chemical product set forth in claim 16, with the addition that the sugar with which the calcium hydroxide is mixed is a hexose.

18. The chemical product set forth in claim 16, with the addition that the sugar with which the calcium hydroxide is mixed is dectrose.

19. A chemical product suitable for intravenous injection in the treatment of diseases where calcium is indicated, comprisin the result obtained by mixing calcium hy. roxide with a solution of a sugar having a free aldehyde or ketone group, in the proportion of at least one part by weight of calcium hydroxide to fifteen parts of sugar, and permitting partial degradation of the su at to a point where destructive action of t e result on the vein-walls is substantially eliminated but the therpeutic efi'ect of the calcium is largely retained.

20. The chemical product set forth in claim 19, with the addition that the sugar with which the calcium hydroxide is mixed is a hexose.

21. The chemical product set forth in claim 19, with the addition that the sugar with which the calcium hydroxide is mixed is dextrose.

In witness whereof, I, GUY VAN SooYoo, have hereunto set my hand at Salt Lake City, Utah, this 23 day of April, 1924.

GUY VAN SCOYOC.

In Witness whereof, I, HENRY L. WEBB- BEIN, have hereunto set 111 band at Indianapolis, Indiana, this 29th ay of April, 1924.

HENRY L. WEHBBEIN.

ciently far to substantially eliminate the objectionable effects of the calcium on the vein-walls but not sufliciently far to destroy the beneficial efi'ects of the calcium on the disease.

12. The method set forth in claim 1, with the addition that the sugar used is dextrose, and that the injection is made when the degradation ot' the dextose has continued sufliciently far to substantially eliminate the objectionable ellects of the calcium on the vein- Walls but not sufliciently far to destroy the beneficial effects Jf the calcium on the disease.

13. A chemical product, comprising the result obtained by mixing calcium hydroxide with a solution of a sugar having a free aldehyde or ketone group, in the proportion of at least one part by weight of calcium hydroxide to fifteen parts of sugar, and ermitting degradation to proceed under eat until such result has an alkalinity of less than one-half of the alkalinity of the com position at the start of the degradation.

14. The chemical product set forth in claim 13, with the addition that the sugar with which the calcium hydroxide is mixed is a hexose.

15. The chemical product set forth in L claim 13, with the addition that the sugar with which the calcium hydroxide is mixed is dextrose.

16. A chemical product, comprising the result obtained by mixing calcium hydroxide with a solution of a sugar having a free aldehyde or ketone group, in the proportion of at least one part by weight of calcium hydroxide to fifteen parts of sugar, and p mittin degradation to proceed until such result as an alkalinity less than one-half of the alkalinity of the composition at the start of the degradation.

17. The chemical product set forth in claim 16, with the addition that the sugar with which the calcium hydroxide is mixed is a hexose.

18. The chemical product set forth in claim 16, with the addition that the sugar with which the calcium hydroxide is mixed is dectrose.

19. A chemical product suitable for intravenous injection in the treatment of diseases where calcium is indicated, comprisin the result obtained by mixing calcium hy roxide with a solution of a sugar having a free aldehyde or ketone group, In the proportion of at least one part by weight of calcium hydroxide to fifteen parts of sugar, and permitting partial degradation of the su ar to a point where destructive action of t e result on the vein-walls is substantially eliminated but the therpeutic efi'ect of the calcium is largely retained.

20. The chemical product set forth in claim 19, with the addition that the sugar with which the calcium hydroxide is mixed is a hexose.

21. The chemical product set forth in claim 19, with the addition that the sugar with which the calcium hydroxide is mixed is dextrose.

In witness whereof, 1, GUY VAN Scoroc, have hereunto set my hand at Salt Lake City, Utah, this 23 day of April, 1924.

GUY VAN SCOYOC.

In witness whereof, I, HENRY L. WEHR- BEIN, have hereunto set my hand at Indianapohs, Indiana, this 29th day of April, 1924.

HENRY L. WEHRBEIN.

Certificate of Correction.

Patent No. 1,649,269.

GUY VAN scoYoc ET AL.

Granted November 15, 1927, to

It is hereby certified that error appears in the printed specification f the above numbered patent requiring correction as follows: Page 3, line- 50, claim 18, for the misspelled word dectrose read dextrose, same page, line 66, claim 20, for the misspelled word hydroxide read hydmmkle; and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 13th day of December, A. D. 1927.

[sun] M. J. MOORE, Acting Commissioner of Patents.

7 Certificate of Correction. Patent No. 1,649,269. Granted November 15, 1927, to GUY VAN SCOYOC ET AL.

It is hereby certified that error appears in the printed specification of the abovenumbered patent requiring correction as follows: Page 3, line 50, claim 18, for the misspelled word dectrose read dextrose; same page, line 66, claim 20, for the misspelled word hydroxide read hji dmwilie; and that the said Letters Patent should be read with these corrections therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 13th day of December, A. D. 1927.

[sun] M. J. MOORE.

Acting Commissioner of Patents. 

